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. 2020 May 20;12(5):465.
doi: 10.3390/pharmaceutics12050465.

Fabrication of Transgelosomes for Enhancing the Ocular Delivery of Acetazolamide: Statistical Optimization, In Vitro Characterization, and In Vivo Study

Eman A Mazyed  1 , Abdelaziz E Abdelaziz  1
Affiliations

Fabrication of Transgelosomes for Enhancing the Ocular Delivery of Acetazolamide: Statistical Optimization, In Vitro Characterization, and In Vivo Study

Eman A Mazyed et al. Pharmaceutics. .

Abstract

Acetazolamide (ACZ) is a potent carbonic anhydrase inhibitor that is used for the treatment of glaucoma. Its oral administration causes various undesirable side effects. This study aimed to formulate transgelosomes (TGS) for enhancing the ocular delivery of ACZ. ACZ-loaded transfersomes were formulated by the ethanol injection method, using phosphatidylcholine (PC) and different edge activators, including Tween 80, Span 60, and Cremophor RH 40. The effects of the ratio of lipid to surfactant and type of surfactant on % drug released after 8 h (Q8h) and entrapment efficiency (EE%) were investigated by using Design-Expert software. The optimized formula was formulated as TGS, using poloxamers as gelling agents. In vitro and in vivo characterization of ACZ-loaded TGS was performed. According to optimization study, F8 had the highest desirability value and was chosen as the optimized formula for preparing TGS. F8 appeared as spherical elastic nanovesicles with Q8h of 93.01 ± 3.76% and EE% of 84.44 ± 2.82. Compared to a free drug, TGS exhibited more prolonged drug release of 71.28 ± 0.46% after 8 h, higher ex vivo permeation of 66.82 ± 1.11% after 8 h and a significant lowering of intraocular pressure (IOP) for 24 h. Therefore, TGS provided a promising technique for improving the corneal delivery of ACZ.

Keywords: ACZ; corneal drug delivery; transfersomes; transgelosomes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
In-vitro release of ACZ-loaded TNVs containing Span 60 (a), Tween 80 (b), and Cremophor RH (c) as edge activators.
Figure 2
Figure 2
The effect of different independent variables on Q8h of ACZ-loaded TNVs.
Figure 3
Figure 3
The effect of different independent variables on EE% of ACZ-loaded TNVs.
Figure 4
Figure 4
Linearity plots of ACZ-loaded TNVs shown as observed versus predicted values (a) Y1 and (b) Y2.
Figure 5
Figure 5
The overall desirability of ACZ-loaded TNVs as a function of independent variables (a) the ratio of lipid to surfactant and (b) the type of surfactant.
Figure 6
Figure 6
Particle size distribution curve (a) and zeta potential (b) of the optimized ACZ transfersomal formula (F8).
Figure 7
Figure 7
Scanning electron micrograph of the optimized ACZ transfersomal formula (F8).
Figure 8
Figure 8
FTIR images of (a) ACZ, (b) PC, (c) Cremophor RH, (d) the plain transfersomes, and (e) optimized transfersomal formula.
Figure 9
Figure 9
DSC thermogram of (a) ACZ, (b) PC, (c) Cremophor RH, (d) the plain transfersomes, and (e) optimized transfersomal formula.
Figure 10
Figure 10
Thixotropic behavior of ACZ-loaded TGS (up and down curves) at 37 ± 0.5 °C.
Figure 11
Figure 11
In vitro release profile of ACZ-loaded TGS, ACZ-loaded TNVs, and ACZ aqueous dispersion (n = 3).
Figure 12
Figure 12
Ex vivo corneal permeation profile of ACZ-loaded TGS, ACZ-loaded TNVs, and ACZ aqueous dispersion (n = 3).
Figure 13
Figure 13
IOP-lowering effect of ACZ-loaded TGS compared to TNVs, free drug suspension, and marketed product (n = 3); dose of different formulations is equivalent to 500 µg of ACZ. Abbreviation: IOP, intraocular pressure; TGS, transgelosome; TNVs, transfersomal nanovesicles.
Figure 14
Figure 14
ACZ aqueous humor concentration profile after intraocular administration of different formulations (n = 3).
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